Diisopropylethylamine → 3-(3,3-difluoroazetidine-1-carbonyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde

HRID 245483Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245483
C(N(C(C)C)CC)(C)C.[CH3:10][C@H:11]1[O:16][C@H:15]([CH3:17])[CH2:14][NH:13][CH2:12]1.[F:18][C:19]1([F:38])[CH2:22][N:21]([C:23]([C:25]2[C:29]3[CH:30]=[C:31]([CH:36]=[O:37])[C:32](F)=[C:33]([F:34])[C:28]=3[O:27][N:26]=2)=[O:24])[CH2:20]1>C(#N)C.O.[Cl-].[Na+].O>[F:38][C:19]1([F:18])[CH2:20][N:21]([C:23]([C:25]2[C:29]3[CH:30]=[C:31]([CH:36]=[O:37])[C:32]([N:13]4[CH2:14][C@@H:15]([CH3:17])[O:16][C@H:11]([CH3:10])[CH2:12]4)=[C:33]([F:34])[C:28]=3[O:27][N:26]=2)=[O:24])[CH2:22]1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 11137133trans-2,6-DimethylmorpholineHCID 866580973-(3,3-Difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde2×

Produkt 1

HCID 866580983-(3,3-difluoroazetidine-1-carbonyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

Diisopropylethylamine (1.432 ml, 8.20 mmol) and (2R,6R)-2,6-dimethylmorpholine (1.027 ml, 8.20 mmol) were added to a solution of 3-(3,3-difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde (Intermediate 241, 1.906 g, 6.31 mmol) in acetonitrile (50 ml). The reaction was stirred at reflux for 20 hours. The reaction was cooled to room temp, diluted with water and brine and extracted twice with ethyl acetate. The organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of DCM to ethyl acetate. Fractions were combined and concentrated to give the title compound.

Aufarbeitung

  1. temperatureat reflux for 20 hours
  2. extractionextracted twice with ethyl acetate
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-6bf58c84431b4e7ab05ff7e905820f61
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

Notizen zur Reaktion

Wird geladen…